Sixty percent of glaucoma patients who have filtration surgery encounter complications related to natural wound healing. A common short-term complication is occlusion of the filtering bleb within 2 to 6 months after surgery. This complication occurs when the natural wound healing response is too extensive. Antimetabolite drugs are therefore used at the time of surgery to control the early wound healing response. However the control is inexact and there is increased risk of hypotony. A common long-term complication is failure of the filtering bleb 2 to 4 years after surgery due to occlusion by dense collagen scars which result from the continued activation of the wound healing response. The proposed research employs the tools of polymer chemistry and biomedical engineering to address this problem of short-term and long-term control of the wound healing response at the filtration site. The objectives of this materials science research project are 1) to define the optimum parameters for controlled release of antimetabolite drugs to control wound healing; 2) to evaluate whether long-term, low-level activation of the wound healing response is a major cause of late failure of glaucoma filtering blebs; and 3) to determine whether prosthetic implants with posterior porous cellular ingrowth surfaces can decrease the micromovement of the implants, thereby minimizing the long-term foreign body responses that stimulate wound healing and may lead to increased collagen scars and fibrous capsule thickening. Specific experiments are designed to: 1) verify that controlled release of an antimetabolite from the biodegradable plug can decrease the initial wound healing response in the filtering blebs of various types of glaucoma filtering surgeries; and 2) evaluate the intermediate and long-term wound healing responses around immobilized versus conventional tube and seton plate implants. Methodology includes fluorophotometric (aqueous flow), histologic (fibrous capsule size and collagen fiber diameter), immunohistochemical (relative quantities of macrophages, fibronectin, and fibroblasts; type of collagen present), non- radioactive in situ hydridization (types l and Ill collagen mRNA), and immunochemical (interleukin I) techniques. The results of these studies will provide insight into the processes involved in the success and failure of filtering surgery, as well as provide a potential solution to the problems associated with the surgical treatment of complicated glaucoma.